There have been many recent advances in the veterinary sciences and veterinary pharmacology that have resulted in the growth and development of larger, healthier and heartier, bovine, porcine, ovine and equine species. Particularly with respect to the bovine, ovine and porcine groups, the need to feed the world's population through the production of meat provides the impetus to raise domestic animals that grow as quickly and as large as possible.
Anabolic agents, are widely used to promote the growth of cattle and other domestic animals and stimulated growth promotion is desirable among the cattle farmers because it maximizes both rate of weight gain and the absolute amount of weight gain per average amount of food consumed, which is termed feed efficiency. Generally, steroids are supplied to the animal in the form of a bio-degradable or non-biodegradable, implantable, time release pellet(s) which is injected under the skin using an implant device. These have been proven to be successful; however, the animals may have to be implanted 2-4 times during their growth period.
The implant devices used for the subcutaneous delivery of these steroid pellets consist of a housing in the shape of a pistol with a handle, a hollow needle for injecting the pellet into the body of the animal located at the front side of the housing, and a push-rod. The push-rod can be slid into this hollow needle and is supported in the housing so as to be displaceable longitudinally. A chamber is provided in the housing and is attached to the needle. A magazine containing the pellets is inserted and displaceable therein. A longitudinally displaceable press-back device (spring ejector) is arranged in the housing parallel to the push-rod and hollow needle in the housing. The push-rod and press-back device are moved by a driving mechanism which is similarly provided in the housing and which can be set in motion by the operating lever (trigger) fastened to the handle. This engages the driving mechanism and press-back device via a toothed segment coupled with the operating lever and a toothed wheel engaging the press-back device and push-rod. Such a device design is described, for example, in U.S. Pat. No. 5,514,101.
Zeranol (Formula I, CAS Registry Number: 26538-44-3) is an anabolic agent which has shown impressive results in the promotion
of weight gain and growth in cattle. Zeranol, a resorcylic acid lactone derivative, has shown to be a positive influence on dynamic protein metabolism. However, during the growth and development of the cattle, current formulations containing zeranol or other such anabolic agent must be administered at least twice over the 170 day growth and development period for optimal results. Obviously, this necessitates bringing cattle in from the fields, reinjecting the implant and transporting them out again which is a laborious and time-consuming process.
It has been determined that zeranol and other anabolic agents provide the best growth and weight gain results when administered early on and throughout the animal's growth cycle. This would require a dual immediate-release/sustained-release formulation which has been hereinbefore not possible.
U.S. Pat. No. 5,643,595 to Lewis discloses and claims a delivery system for veterinary growth promotants consisting of a biodegradable polymeric matrix that contains a steroid growth promotant and an antibiotic. The steroid growth promotant may consist of zeranol which is formulated within sustained-release microparticles consisting of homopolymers or copolymers of lactic and/or glycolic acid. Other biodegradable polymers used in the sustained-release formulations include polycaprolactone, polydioxonene, polyorthoesters, polyanhydrides, waxes, casein and mixtures thereof.
U.S. Pat. No. 5,427,796 also to Lewis discloses a method for increasing animal growth comprising the administration of an anabolic steroid such as zeranol in a biodegradable microparticle delivery system that releases the drug in a multiphasic manner. Drug delivery duration allegedly lasts up to 200 days. The same polymers are used in Lewis's other patents noted above and below.
U.S. Pat. Nos. 5,419,910 and 5,288,496 to Lewis also disclose and claim a microparticulate sustained-release delivery system for promoting growth in animals. The microparticles are comprised of a biodegradable polymeric matrix such as poly-d,l-lactic acid, polyglycolic acid and the like. The microparticles separately encapsulate a steroid growth promotant and an antibiotic. Zeranol, among other anabolic steroids, is disclosed as one of the useful actives that result in increased bulk weight and growth.
U.S. Pat. No. 4,874,612 to Deasy discloses a multi-component implant for the sustained-release, long-term delivery of pharmaceutical agents to humans and animals for the treatment of vitamin deficiencies, hormone replacement therapy, cancer therapy, infection and the like. Preferably, the biodegradable polymers comprising the implants are used to deliver animal growth promotants which contain anabolic steroids such as zeranol as well as their combinations. The matrix used to make the implants consists of lactic acid/glycolic acid copolymers.
U.S. Pat. No. 4,191,741 to Hudson et al discloses and claims polymeric implants for the long-term sustained-release of anabolic agents to ruminant animals. The steroids can be administered alone or in combination, one of which is estradiol. Zeranol is not specifically disclosed as one of these agents.
In fact, the use of biodegradable particles for the long-term, sustained-release of anabolic steroids and other pharmaceutical actives is known in the art. See for example, U.S. Pat. Nos. 4,683,288; 4,677,191; 4,675,189; 4,542,025; 4,530,840; 4,489,055 and 4,389,330.
Unfortunately, not all of the prior art delivery systems enable zeranol to be administered in a way that maximizes the growth and weight gain potential that exists. Whereas zeranol and other anabolic agents must be administered two to four times during the growth phase of the animal, it would be most advantageous to provide a formulation that need only be administered once.
It is an object of the present invention to provide an anabolic implant formulation for increased growth and weight gain significantly greater than that achieved by animals given other steroid therapies and those given none at all. It is a further object of the present invention to provide an anabolic implant formulation that is given only once during the growth phase of the animal yet provides both immediate and sustained, long-term administration of the drug throughout the growth period for optimal growth and weight gain.